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Reciprocal regulation of the Il9 locus by counteracting activities of transcription factors IRF1 and IRF4

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  • Lucia Campos Carrascosa

    (Institute for Medical Microbiology and Hospital Hygiene, University of Marburg)

  • Matthias Klein

    (Institute for Immunology, University Medical Center Mainz)

  • Yohko Kitagawa

    (Laboratory of Experimental Immunology, Immunology Frontier Research Center, Osaka University)

  • Christina Lückel

    (Institute for Medical Microbiology and Hospital Hygiene, University of Marburg)

  • Federico Marini

    (Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), University Medical Center Mainz)

  • Anika König

    (Institute of Pathology, University of Würzburg)

  • Anna Guralnik

    (Institute for Medical Microbiology and Hospital Hygiene, University of Marburg)

  • Hartmann Raifer

    (Institute for Medical Microbiology and Hospital Hygiene, University of Marburg)

  • Stefanie Hagner-Benes

    (Institute for Laboratory Medicine and Pathobiochemistry, University of Marburg)

  • Diana Rädler

    (University Childrens’s Hospital Munich, LMU Munich)

  • Andreas Böck

    (University Childrens’s Hospital Munich, LMU Munich)

  • Cholho Kang

    (Institute for Medical Microbiology and Hospital Hygiene, University of Marburg)

  • Michael Lohoff

    (Institute for Medical Microbiology and Hospital Hygiene, University of Marburg)

  • Holger Garn

    (Institute for Laboratory Medicine and Pathobiochemistry, University of Marburg)

  • Bianca Schaub

    (University Childrens’s Hospital Munich, LMU Munich)

  • Friederike Berberich-Siebelt

    (Institute of Pathology, University of Würzburg)

  • Shimon Sakaguchi

    (Laboratory of Experimental Immunology, Immunology Frontier Research Center, Osaka University)

  • Tobias Bopp

    (Institute for Immunology, University Medical Center Mainz)

  • Magdalena Huber

    (Institute for Medical Microbiology and Hospital Hygiene, University of Marburg)

Abstract

The T helper 9 (Th9) cell transcriptional network is formed by an equilibrium of signals induced by cytokines and antigen presentation. Here we show that, within this network, two interferon regulatory factors (IRF), IRF1 and IRF4, display opposing effects on Th9 differentiation. IRF4 dose-dependently promotes, whereas IRF1 inhibits, IL-9 production. Likewise, IRF1 inhibits IL-9 production by human Th9 cells. IRF1 counteracts IRF4-driven Il9 promoter activity, and IRF1 and IRF4 have opposing function on activating histone modifications, thus modulating RNA polymerase II recruitment. IRF1 occupancy correlates with decreased IRF4 abundance, suggesting an IRF1-IRF4-binding competition at the Il9 locus. Furthermore, IRF1 shapes Th9 cells with an interferon/Th1 gene signature. Consistently, IRF1 restricts the IL-9-dependent pathogenicity of Th9 cells in a mouse model of allergic asthma. Thus our study reveals that the molecular ratio between IRF4 and IRF1 balances Th9 fate, thus providing new possibilities for manipulation of Th9 differentiation.

Suggested Citation

  • Lucia Campos Carrascosa & Matthias Klein & Yohko Kitagawa & Christina Lückel & Federico Marini & Anika König & Anna Guralnik & Hartmann Raifer & Stefanie Hagner-Benes & Diana Rädler & Andreas Böck & C, 2017. "Reciprocal regulation of the Il9 locus by counteracting activities of transcription factors IRF1 and IRF4," Nature Communications, Nature, vol. 8(1), pages 1-12, August.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15366
    DOI: 10.1038/ncomms15366
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